The objective of this research proposal is to determine the influence of the host's immune response on the composition and population levels of the indigenous bacteria colonizing its gastrointestinal (GI) tract. Immunofluorescence methods have been developed to demonstrate specific antibodies (especially secretory IgA) in intestinal secretions adhering to the surfaces of indigenous bacteria in vivo. Radioimmunoassays also will be developed to quantitate these specific antibodies in intestinal secretions reacting with antigens of these indigenous bacteria. These techniques will be employed to determine whether or not specific local immunity reduces the population levels of certain oxygen-sensitive anaerobic bacteria in the mouse GI tract. A gnotobiotic mouse model has been developed demonstrating bacterial antagonism of an oxygen-sensitive Bacteroides sp. by oxygen-sensitive Eubacterium sp. and Fusobacterium sp. This model will be used to determine whether or not specific local immunity and bacterial antagonism can act synergistically in vivo to reduce the population levels of the indigenous Bacteroides. Local immunity may have a greater reducing effect on population levels of Bacteroides already lowered by bacterial antagonism than on the high population levels of Bacteroides found in monoassociated gnotobiotic mice. Finally, the local immune responses of gnotobiotic mice raised in an environment containing certain indigenous bacteria will be compared with the responses of mice raised in the germfree state. Gnotobiotic mice reared from birth in the presence of particular indigenous bacteria may be immunologically tolerant to vaccination with these bacterial antigens compared with the immune responses of germfree mice raised in the absence of these bacteria but vaccinated with these same antigens.